Operation control method of detection item and sample analyzer

Abstract

The invention provides a detection item operation control method and a sample analyzer. The operation control method of the detection items is applied to a sample analyzer and comprises the following steps: acquiring an execution list of at least two detection items; judging whether the execution list contains a specified detection item pair or not; and when it is judged that the execution list contains the specified detection item pair, controlling two detection items in the specified detection item pair to be executed according to a preset sequence. Therefore, the two detection items in the specified detection item pair can be executed according to the preset sequence.

Description

Technical Field

[0001] The present invention relates to the technical field of sample analysis, and in particular to an operation control method for a detection item and a sample analyzer. Background Art

[0002] Sample analyzers, such as biochemical analyzers and chemiluminescence analyzers, are mainly used to detect specific markers in body fluids (such as blood). Sample detection requires cooperation with special reagents. By testing the mixture formed by the sample and the reagent, the concentration of the specific marker can be obtained.

[0003] Sample analyzers generally use the pipette needle of the pipette to absorb the reagent and inject the reagent into the sample to perform the test. Between different test items, the pipette needle is cleaned with a wash solution. However, it is difficult to ensure 100% cleanliness with this kind of cleaning, and there must be a certain amount of residue. For most test items, this low residue usually does not cause the result of the next test item to be wrong, so it can be ignored.

[0004] However, for some highly contaminating test items, conventional washing solutions are not sufficient to reduce the carryover rate to a sufficiently low level, so that strong cross contamination will occur when the reagents for the next test item are drawn, resulting in distorted results for the test item.

[0005] There is no clear standard to define which test items are highly contaminating items at present. Professional inspectors can only determine highly contaminating items based on experience and on-site practice and arrange the pipette needle to perform enhanced cleaning action between the test items that are prone to cross contamination, that is, use a special washing liquid different from conventional washing liquid (such as an organic washing liquid with high alcohol content or a special washing liquid of strong alkalinity\strong acidity) to clean the pipette needle. In extreme cases, it is even necessary to perform two cleanings, that is, a strengthened cleaning and a pure water rinse. This enhanced cleaning is obviously more expensive than conventional cleaning, and this enhanced cleaning action requires more execution time than conventional cleaning action. However, this special washing liquid is due to the strong effect on the biological components of the detection reagent, and thus when using the special washing liquid to clean the pipette needle, it is necessary to avoid the residue of the special washing liquid, such as by using pure water rinse again and controlling the special washing liquid dosage to avoid. This has caused further residual risks and increased costs.

[0006] Therefore, a new method is needed to reduce or avoid cross contamination of pipette needles, while avoiding the use of special washing solutions as much as possible, reducing the cost and time consumption. Summary of the invention

[0007] The main purpose of the present invention is to provide an operation control method for detection items and a sample analyzer, so that the sample analyzer can determine whether cross contamination will occur between detection items, and automatically avoid cross contamination between detection items by adjusting the execution list of the detection items when it is determined that cross contamination will occur, while saving manpower and improving detection efficiency and the accuracy of detection results.

[0008] In a first aspect, the present invention provides an operation control method for a detection project, comprising: obtaining an execution list for at least two detection projects; determining whether the execution list contains a specified detection project pair; and when it is determined that the execution list contains a specified detection project pair, controlling the two detection projects in the specified detection project pair to be executed in a preset order.

[0009] In one embodiment, obtaining an execution list for at least two detection items includes: obtaining an execution list for at least two detection items according to identification data of the sample to be detected.

[0010] In one embodiment, determining whether the execution list contains a specified detection item pair includes: obtaining a preset list of specified detection item pairs; matching any two detection items in the execution list with the preset list of specified detection item pairs, and determining whether the execution list contains a specified detection item pair based on the matching result.

[0011] In one embodiment, when the execution list includes the designated detection item pair, the designated detection item pair is executed in the preset order only when two detection items in the designated detection item pair are adjacent to each other in the execution list.

[0012] In one embodiment, the designated detection item pair list includes: multiple groups of designated detection item pairs and a preset order for executing the two detection items corresponding to each group of designated detection item pairs; controlling the two detection items in the designated detection item pair to be executed according to the preset order includes: controlling the two detection items in the designated detection item pair to be executed according to the corresponding preset order in the designated detection item pair list, and the execution order of other detection items in the execution list remains unchanged.

[0013] In one embodiment, when the two test items in the designated test item pair are controlled to be performed in a preset order, the pipette does not perform enhanced washing between sequentially aspirating the test reagents for the two test items.

[0014] In one embodiment, the designated detection item pair includes: two detection items with cross contamination; wherein the cross contamination includes mutual consumption between detection reagents, and the mutual consumption includes at least one of the following: mutual binding and mutual reaction.

[0015] In one embodiment, the two detection items in the designated detection item pair include an antibody detection item for detecting antibodies and an antigen detection item for detecting antigens corresponding to the antibodies. The preset sequence includes: executing the antibody detection item first and then executing the antigen detection item.

[0016] In one embodiment, when the designated test item pair includes hepatitis B virus e antibody detection and hepatitis B virus e antigen detection, the preset order includes: performing hepatitis B virus e antibody detection first, and then performing hepatitis B virus e antigen detection.

[0017] In one embodiment, when the designated test item pair includes hepatitis B virus surface antibody detection and hepatitis B virus surface antigen detection, the preset order includes: performing hepatitis B virus surface antibody detection first, and then performing hepatitis B virus surface antigen detection.

[0018] In a second aspect, the present invention provides a readable storage medium having a computer program stored thereon, and when the computer program is executed, the steps of the operation control method of the detection item as described in any of the above embodiments are executed.

[0019] In a third aspect, the present invention provides a sample analyzer, comprising: a reagent unit, comprising a reagent chamber for storing a detection reagent kit and a pipette for aspirating the detection reagent; a sample unit, comprising a sample chamber for storing the sample and a sample loading arm for aspirating the sample; an analysis unit, for analyzing a mixture of the sample and the reagent; a control device, for controlling the sample analyzer, wherein the control device comprises a database, in which a list of specified detection item pairs is stored; the control device also comprises the readable storage medium as described above, for executing the steps of the operation control method of the detection item according to the present invention.

[0020] In a fourth aspect, the present invention provides a method for using a hepatitis B detection reagent combination, the hepatitis B detection reagent combination comprising: a hepatitis B virus surface antigen detection reagent, a hepatitis B virus surface antibody detection reagent, a hepatitis B virus e antigen reagent, and a hepatitis B virus e antibody reagent; wherein the hepatitis B virus surface antibody detection reagent is used before the hepatitis B virus surface antigen detection reagent, and the hepatitis B virus e antibody reagent is used before the hepatitis B virus e antigen reagent.

[0021] Through the operation control method of the detection items of the present invention, the sample analyzer can autonomously judge whether there may be cross contamination between the detection reagents. By judging whether there is a designated detection item pair in the detection items to be executed, and when there is a designated detection item pair, controlling the two detection items in the designated detection item pair to be executed in a preset order, the sample analyzer can achieve separate processing of two detection items in the designated detection item pair that may have cross contamination, thereby reducing the mutual influence between the detection reagents used for each detection item or preventing the reagents used for the detection items from affecting each other, which is conducive to improving the accuracy of the detection results or obtaining the desired detection results and shortening the cleaning procedures between the cross-contamination items, thereby saving costs.

[0022] Through the method of this embodiment, in particular, the execution order of the antibody detection project including detecting antibodies and the antigen detection project including detecting antigens corresponding to the antibodies is limited, which can effectively control the mutual influence between the detection reagents used in each detection project, thereby facilitating obtaining the desired detection results. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0024] Figure 1 is a flow chart of a method for controlling the operation of a detection item according to an exemplary embodiment of the present application;

[0025] Figure 2 is an exemplary diagram of a sample analyzer according to an exemplary embodiment of the present application. DETAILED DESCRIPTION

[0026] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0027] In this application, "enhanced cleaning" refers to a cleaning procedure different from the normal cleaning of the sample analyzer, which uses a special cleaning solution different from the normal cleaning. In a sample analyzer equipped with enhanced cleaning, both normal cleaning and enhanced cleaning procedures may be equipped at the same time.

[0028] Figure 1A flow chart of an operation control method for a detection item according to an exemplary embodiment of the present application is shown. The operation control method can be run on any sample analyzer that uses a detection reagent to analyze a blood sample. For example, the sample analyzer can be a biochemical analyzer, a chemiluminescence analyzer, etc. Further, the sample analyzer can be a sample analyzer based on different detection methodologies, such as a biochemical analyzer based on latex turbidimetric detection, a chemiluminescence analyzer based on enzyme-linked immunosorbent assay, and a chemiluminescence analyzer based on photoinduced chemiluminescence.

[0029] The following is based on Figure 2 The sample analyzer shown illustrates Figure 1 Details of the operation control method. Figure 2 The sample analyzer shown is designed based on photochemiluminescence method and uses a corresponding detection kit of the photochemiluminescence method.

[0030] Photochemiluminescence is a homogeneous chemiluminescence method that detects the concentration of the substance to be tested in the blood sample to be tested based on the interaction between biological molecules. The detection kit of the photochemiluminescence method includes a variety of reagents, which include photosensitive microspheres and luminescent microspheres. Usually, the antigen or antibody used to label the substance to be tested is coated with the luminescent microsphere to prepare a first reagent containing luminescent microspheres. The surface of the photosensitive microspheres is coated with avidin to prepare a second reagent. During the detection process, the first reagent containing the luminescent microspheres and the second reagent are combined with the sample to be tested in turn. When the sample contains the substance to be tested, the photosensitive microspheres and the luminescent microspheres are combined within a certain range through the biotin-avidin reaction system to generate the transfer of ion oxygen energy and emit a light signal, thereby detecting the sample to be tested. Among them, the photosensitive microspheres are filled with photosensitive compounds, and the luminescent microspheres are filled with luminescent compounds and lanthanide elements. Under the excitation of red laser (600-700nm), the photosensitive microspheres release high-energy singlet oxygen ions (4μS), and their propagation distance is about 200nm. When the distance between the photosensitive microsphere and the luminescent microsphere is close enough, the singlet oxygen ions released by the photosensitive microsphere can reach the luminescent microsphere and emit 520-620nm high-energy light through a series of chemical reactions, which is detected by the instrument's detection unit. When the sample does not contain the substance to be tested, the two microspheres cannot form an immune complex, the distance between the two microspheres exceeds the propagation range of ion oxygen, and the ion oxygen is quickly quenched in the liquid phase, and no high-energy red light is generated during detection.

[0031] The size of the microspheres of the photochemiluminescence detection reagent is at the nanometer level, so they have a large specific surface area after coating, which can effectively avoid the steric hindrance effect and improve the detection sensitivity.

[0032] Although the present application uses a photochemiluminescence analyzer and a photochemiluminescence detection reagent as an example, the present application is not limited thereto, but can be run on any sample analyzer that uses a detection reagent to analyze a blood sample, as long as the microspheres contained in the detection reagent are coated with an antigen or antibody, or a biotin-labeled antigen or antibody.

[0033] Figure 2 The sample analyzer 1 shown has a reagent unit, which includes a reagent compartment 109 for storing the detection reagent required for the detection and a pipette 108 for absorbing the detection reagent, wherein the detection reagent is, for example, a hepatitis B virus surface antigen reagent, a hepatitis B virus surface antibody reagent, a hepatitis B virus e antigen reagent, and a hepatitis B virus e antibody reagent. The sample analyzer 1 also has a sample unit, which includes a sample compartment 104 for storing a blood sample to be detected and a sample loading arm 106 for absorbing the sample, wherein the blood sample is, for example, a patient blood sample or an animal blood sample. A scanner (not shown) for reading the sample code is provided in the sample compartment 104. The sample analyzer 1 also has an analysis unit, which is used to analyze a mixture of the sample and the reagent. The analysis unit includes an incubation tray 107, which is used to carry the reaction cup required for the detection and provide the temperature required for the reaction, such as heating the reaction container by a heating plate. The analysis unit also includes a detection unit not shown, which detects the signal generated by the reaction liquid in the reaction cup. The sample analyzer 1 further comprises a cup organizer 102 , which is used to store reaction cups required for detection and analysis and to transfer the reaction cups to an incubation tray 107 .

[0034] The sample analyzer 1 is equipped with a control device 101, which controls the execution of the actions of each component. The control device 101 obtains a sample code from a sample bin 104. The sample code is a specific identifier used to identify a sample. After obtaining the sample code, the control device obtains the test items of the sample to be tested according to the sample code. The user can input the test items corresponding to the sample code into the sample analyzer in advance. The test items can also be obtained by the control device 101 from a superior information management system (such as a laboratory information management system LIS, or a hospital information management system HIS) that is communicatively connected to the sample analyzer.

[0035] The samples to be tested are usually put into the sample bin in batches, for example, five or ten at a time. In addition, each sample to be tested may correspond to multiple items to be tested, for example, one sample needs to be tested for three infectious diseases. Therefore, the test items obtained by the control device are usually in the form of an execution list. The execution list includes the sample codes of all samples to be tested and the execution order of the corresponding test items. In the execution list, the test items can be arranged in units of samples, that is, all the test items of one sample are executed first, and then all the test items of the next sample are executed.

[0036] The control device determines the final execution order of each detection item and controls each component of the sample analyzer to perform corresponding actions.

[0037] For example, the sample loading arm 106, after being equipped with a disposable pipette tip of the pipette tip bin 105, draws the blood sample to be tested from the sample bin 104 and transfers the blood sample to an empty reaction cup of the incubation tray 107. The reagent arm 108 draws the required detection reagent from the reagent bin 109 according to the execution list and transfers the reagent to the reaction cup on the incubation tray 107 to which the blood sample has been added.

[0038] After the reagent arm 108 absorbs and transfers a detection reagent each time, it is cleaned with the help of the conventional washing solution provided by the liquid path module 103. After cleaning, the reagent arm 108 absorbs and transfers the next required detection reagent.

[0039] In the related art, the execution order of the test items is executed in the order in which the sample analyzer receives the test items, that is, the execution order is arranged in the control device in the order in which the test items are received.

[0040] However, in this embodiment, after receiving the task of the test items, it is determined whether any two test items are cross-contamination related items. If so, the related test items are controlled to run in a specified order.

[0041] like Figure 1 As shown, the method of this embodiment may include:

[0042] S110: Obtaining an execution order of at least two detection items;

[0043] S120: Determine whether the execution sequence includes a specified detection item pair;

[0044] S130: When it is determined that the execution sequence includes a designated detection item pair, two detection items in the designated detection item pair are controlled to be executed according to a preset sequence.

[0045] Through the above steps, when the at least two detection items obtained include a designated detection item pair, the two detection items in the designated detection item pair are controlled to be executed in a preset order, so that if the two detection items in the designated detection item pair are not arranged in the preset order according to the current execution order, the execution order of the two detection items can be adjusted to the preset order. By controlling the execution order of the two detection items in the designated detection item pair in the execution order, the execution order of the two detection items in the designated detection item pair is processed separately, which can reduce the mutual influence between the various detection items or cause specific mutual influence between the detection items, which is conducive to improving the accuracy of the detection result or obtaining a specific detection result.

[0046] Step S120 further includes: obtaining a preset list of designated detection item pairs; matching any two detection items in the execution list with the preset list of designated detection item pairs, and determining whether the execution list contains the designated detection item pair according to the matching result.

[0047] Here, the list of designated detection items can be pre-set in the database of the sample analyzer. For example, a user or a manufacturer can pre-set a cross contamination list in the computer of the sample analyzer based on experience or based on the performance of the reagents. In this list, the detection items that will cause cross contamination between each other are listed in pairs, that is, the detection reagents used may cross contaminate each other. At the same time, a preset order corresponding to the paired detection items is also stored in the database. The preset order can also be listed in the cross contamination list at the same time.

[0048] After the sample analyzer obtains the execution list, the sample analyzer first retrieves the cross-contamination list and matches any two test items in the execution list with the test items listed in pairs in the cross-contamination list to confirm whether the execution list contains test items that may cause cross-contamination.

[0049] When it is determined that the execution order includes a specified detection item pair, step S130 is performed. That is, it is determined whether the execution order of the two detection items in the execution list is consistent with the preset order. If it is inconsistent, the execution order of the two detection items is adjusted to the preset order. If it is consistent, no adjustment is made. For example, the 4th and 5th detection items in the execution list are detection items that may be cross-contaminated. Upon inquiry, the preset order is that the 5th detection item should be executed before the 4th detection item, then the execution order of the 4th and 5th detection items in the execution list is swapped. For another example, the 6th and 9th detection items in the execution list are detection items that may be cross-contaminated. Upon inquiry, the preset order is that the 6th detection item should be executed before the 9th detection item, then the execution order of the 6th and 9th detection items in the execution list is maintained.

[0050] Preferably, in the case where the execution list includes the designated detection item pair, the designated detection item pair is executed in the preset order only when two detection items in the designated detection item pair are adjacent in the execution list.

[0051] The applicant has found that when the detection reagents used in two test items may cross-contaminate each other, the two test items have the greatest risk of cross-contamination when they are performed adjacent to each other. Therefore, for the adjacent situation, they must be performed strictly in the preset order. However, when the two test items are separated by one or more other test items, the risk of cross-contamination is greatly reduced due to the use of other detection reagents in between, and the execution order may not be adjusted.

[0052] Furthermore, the designated detection item pair list comprises: a plurality of groups of designated detection item pairs and a preset order for executing the two detection items corresponding to each group of designated detection item pairs; controlling the two detection items in the designated detection item pair to be executed according to the preset order comprises: controlling the two detection items in the designated detection item pair to be executed according to the corresponding preset order in the designated detection item pair list, and the execution order of other detection items in the execution list remains unchanged.

[0053] That is to say, the execution order is adjusted only for these two test items. If the preset order is opposite to the order in the received execution list, the two test items are swapped, but other test items are not affected. For example, the order of the execution list is 1->2->3->4->5->6->7. When the 4th and 5th test items in the execution list have a risk of cross contamination, and the preset order is that the 5th test item is before the 4th test item, the execution list is adjusted to 1->2->3->5->4->6->7.

[0054] Furthermore, when the two test items in the designated test item pair are controlled to be executed in a preset order, the pipette does not perform enhanced cleaning between successively drawing the test reagents for the two test items. In other words, when the two test items are executed in a preset order, the risk of cross contamination has been eliminated and the pipette does not need to be enhanced cleaned. Accordingly, the sample analyzer may no longer be equipped with a special washing solution for enhanced cleaning.

[0055] Preferably, the designated detection item pair includes: two detection items with cross contamination; wherein the cross contamination includes mutual consumption between detection reagents, and the mutual consumption includes at least one of the following: mutual binding and mutual reaction.

[0056] In one embodiment, the two detection items in the designated detection item pair include an antibody detection item for detecting antibodies and an antigen detection item for detecting antigens corresponding to the antibodies. When it is determined that the execution list includes the designated detection item pair, the two detection items in the designated detection item pair are controlled to be executed in a preset order, and the preset order includes: and the preset order includes: executing the antibody detection item first, and then executing the antigen detection item.

[0057] The applicant has found that the mechanism of cross contamination is that the components of the detection reagents used will bind and react with each other when added in a certain order, especially in the detection items for detecting antibodies and the detection items for detecting antigens corresponding to antibodies.

[0058] For the diagnosis of some immune diseases, multiple immune markers must be tested to help doctors determine the extent of the disease. For example, for hepatitis B, not only the e antibody in the blood sample should be tested, but also the e antigen. In other words, e antibody detection and e antigen detection should be performed. The detection reagent for detecting antibodies usually contains e antigen so that the corresponding antibody can be detected by the combination of antigen and antibody. The detection reagent for detecting the corresponding antigen usually contains e antibody based on the same principle so that the corresponding antigen can be detected by the combination of antigen and antibody.

[0059] The two detection reagents for detecting antibodies and antigens have a greater risk of cross-contamination because they detect the same diseases and contain reagent components that may bind to each other. Especially when the antigen is detected first and then the antibody corresponding to the antigen is detected, the antigen detection reagent will cause great interference to the antibody detection reagent, resulting in distorted test results.

[0060] After continuous research and multiple experiments, the applicant found that the antibody detection reagent for detecting antibodies and the antigen detection reagent for detecting antigens corresponding to the antibodies no longer cross-contaminate in a specific execution order. The reason is that the affinity of the antibodies in the antigen detection reagent is higher than the affinity of the antibodies in human blood. When the antigen detection reagent is used before the antibody detection reagent, a portion of residual antibodies that have not fully reacted will remain on the reagent needle. When the antibody detection reagent is added, since the affinity of the residual antibodies on the reagent needle is higher than the affinity of the antibodies in the blood sample, the antigens in the antibody detection reagent will react with the participating antibodies first, and then react with the antibodies in the blood sample. This leads to cross contamination.

[0061] The affinity of the antigen in the antibody test reagent is the same as the affinity of the antigen in human blood. Therefore, even if there is a slight residue of antigen in the antibody test reagent, the antibody in the antigen test reagent will not preferentially react with the residual antigen.

[0062] Another important reason is that the number of antigens / antibodies in the reagent has a certain impact on cross contamination. The number of antigens used in the antibody detection reagent is less than the number of antibodies in the antigen detection reagent.

[0063] The number of antibodies and antigens produced in the human body during immunization is not equal, and the number of antibodies is generally less than the number of antigens. Correspondingly, the number of antigens contained in the reagents used to detect antibodies in the human body is also less than the number of antibodies contained in the reagents used to detect antigens in the human body. Therefore, when the antigen detection reagent is used first, antibody residues are likely to occur. However, since the antibody detection reagent contains a smaller number of antigens, antigen residues are not likely to occur.

[0064] Therefore, by performing antibody detection projects prior to antigen detection projects, cross-contamination between the detection reagents used for these two detection projects can be effectively avoided.

[0065] Preferably, when the designated test item pair includes hepatitis B virus e antibody detection and hepatitis B virus e antigen detection, the preset order includes: performing hepatitis B virus e antibody detection first, and then performing hepatitis B virus e antigen detection.

[0066] Preferably, when the designated test item pair includes hepatitis B virus surface antibody detection and hepatitis B virus surface antigen detection, the preset order includes: performing hepatitis B virus surface antibody detection first, and then performing hepatitis B virus surface antigen detection.

[0067] The effect of the technical solution of the present application is explained below based on specific experiments.

[0068] Verification Example 1

[0069] 1. Experimental materials and equipment

[0070] Raw materials: luminescent microspheres (purchased from Platinum Elmer), photosensitive microspheres (purchased from Platinum Elmer), HBsAg antigen (purchased from Feipeng Biotechnology), HBsAg antibody (purchased from Feipeng Biotechnology)

[0071] 2. The coupling process of HBsAg antigen / antibody and receptor particles

[0072] 1) The HBsAg antigen / antibody was dialyzed into 50 mM CB buffer with a pH value of 9.0, and the concentration was measured to be 1 mg / ml.

[0073] 2) Add 0.5 ml of receptor particles and 0.5 ml of HBsAg antigen / antibody obtained in step 1) into a 2 ml centrifuge tube, mix well, add 100 μl of 10 mg / ml NaBH4 solution, and react at 2-8°C for 4 hours.

[0074] 3) After the reaction is complete, add 0.5 ml of 100 mg / ml bovine serum albumin solution and react at 2-8°C for 2 hours.

[0075] 4) After the reaction is completed, the supernatant is discarded by centrifugation, and the suspension is resuspended in 50 mM MES buffer. The centrifugation is repeated four times, and the suspension is diluted to a final concentration of 100 μg / ml to obtain a receptor particle solution coupled with HBsAg antigen / antibody.

[0076] 3. Biotin labeled HBsAg antigen / antibody

[0077] 1) The HBsAg antigen / antibody was dialyzed into 50 mM PBS buffer with a pH value of 7.4, and the concentration was measured to be 1 mg / ml.

[0078] 2) Labeling: Take the processed 1mg / ml HBsAg antigen / antibody and mix them with the prepared 1.997*10 -5 mol / ml Biotin solution, mix quickly according to the volume ratio of 10000:116, and let it react at 2-8℃ for 12-16 hours.

[0079] 3) Dialysis: Place the biotinylated antigen / antibody in a dialysis bag with a molecular weight cutoff of 3500D and dialyze it in a buffer solution with a volume greater than 100 times the volume at 2-8°C. Change the buffer solution twice, with each dialysis lasting 4-5 hours.

[0080] 4) Aspirate the dialyzed biotinylated antigen / antibody and transfer it to a clean centrifuge tube. Take a sample to determine the antigen / antibody concentration and the antigen (or antibody) / biotin ratio. Adjust the biotinylated antigen / antibody concentration to 0.5 mg / ml. Prepare for dilution.

[0081] 4. Reagent preparation process

[0082] 1) Dilute the HBsAg antibody receptor microspheres to 80 μg / ml with PBS buffer as hepatitis B surface antigen reagent 1, and dilute the biotin-labeled HBsAg antibody to 1 μg / ml with PBS buffer as hepatitis B surface antigen reagent 2;

[0083] 2) Dilute the HBsAg antigen receptor microspheres to 100 μg / ml with PBS buffer as hepatitis B surface antibody reagent 1, and dilute the biotin-labeled HBsAg antigen to 1 μg / ml with PBS buffer as hepatitis B surface antibody reagent 2,

[0084] 3) Assemble the HBsAg reagent 1 and the HBsAg reagent 2 into a complete HBsAg reagent, and place them together with the photosensitive microsphere solution in a HBsAg reagent kit.

[0085] 4) Assemble the HBsAg antibody reagent 1 and the HBsAg antibody reagent 2 into a complete HBsAg antibody reagent, and place them together with the photosensitive microsphere solution in a HBsAg antibody kit (HBsAb).

[0086] 5. Experimental data

[0087] Produced by Kemei Diagnostics The Smart photochemiluminescence analyzer was used to test the prepared hepatitis B surface antigen reagent and hepatitis B surface antibody reagent. Commercially available negative samples, positive samples, and gray area samples were used as test samples.

[0088] When the concentration value of the hepatitis B surface antibody reagent is ≥10.00mIU / mL, the sample result is judged as positive; otherwise it is judged as negative; when the concentration value of the hepatitis B surface antigen reagent is ≥0.05IU / mL, the sample result is judged as positive; otherwise it is judged as negative.

[0089] The experimental data are shown in Appendix 1.

[0090]

[0091]

[0092] From the experimental data we can see that:

[0093] 1. When the HBsAg reagent and the HBsAg antibody reagent are tested simultaneously, and the HBsAg antibody reagent is placed before the HBsAg reagent for testing; both sets of reagents are not interfered with, and the test results are similar to those of individual tests.

[0094] 2. When the HBV surface antigen reagent and the HBV surface antibody reagent are tested at the same time, and the HBV surface antigen reagent is placed before the HBV surface antibody reagent, the test result increases significantly, and the HBV surface antibody reagent is interfered by the contamination carried by the reagent.

[0095] Verification Example 2

[0096] 1. Experimental materials and equipment

[0097] Raw materials: luminescent microspheres (purchased from Platinum Elmer), photosensitive microspheres (purchased from Platinum Elmer), HBsAg antigen (purchased from Feipeng Biotechnology), HBsAg antibody (purchased from Feipeng Biotechnology)

[0098] 2. The coupling process of HBeAg antigen / antibody and receptor particles

[0099] 1) The HBeAg antigen / antibody was dialyzed into 50 mM CB buffer with a pH value of 9.0 and the concentration was measured to be 1 mg / ml.

[0100] 2) Add 0.5 ml of receptor particles and 0.5 ml of HBeAg antigen / antibody obtained in step 1) into a 2 ml centrifuge tube, mix well, add 100 μl of 10 mg / ml NaBH4 solution, and react at 2-8°C for 4 hours.

[0101] 3) After the reaction is complete, add 0.5 ml of 100 mg / ml bovine serum albumin solution and react at 2-8°C for 2 hours.

[0102] 4) After the reaction is completed, centrifuge and discard the supernatant, resuspend with 50mM MES buffer, repeat centrifugation and washing four times, and dilute to a final concentration of 100μg / ml to obtain a receptor particle solution coupled with HBeAg antigen / antibody.

[0103] 3. Biotin labeled HBeAg antigen / antibody

[0104] 1) The HBeAg antigen / antibody was dialyzed into 50 mM PBS buffer with a pH value of 7.4 and the concentration was measured to be 1 mg / ml.

[0105] 2) Labeling: Take the treated 1 mg / ml HBeAg antigen / antibody and the prepared 1.997*10-5 mol / ml Biotin solution, mix them at a volume ratio of 10000:116, mix them quickly and let them react at 2-8°C for 12-16 hours.

[0106] 3) Dialysis: Place the biotinylated antigen / antibody in a dialysis bag with a molecular weight cutoff of 3500D and dialyze it in a buffer solution with a volume greater than 100 times the volume at 2-8°C. Change the buffer solution twice, with each dialysis lasting 4-5 hours.

[0107] 4) Transfer the dialyzed biotinylated antigen / antibody to a clean centrifuge tube, take a sample to determine the antigen / antibody concentration and antigen (or antibody) / biotin ratio. Adjust the antigen / antibody concentration to 0.5 mg / ml with biotin label. Prepare for dilution.

[0108] 4. Reagent preparation process

[0109] 1) diluting HBeAg antibody receptor microparticles to 80 μg / ml with PBS buffer as hepatitis B E antigen reagent 1, and diluting biotin-labeled HBeAg antibody to 1 μg / ml with PBS buffer as hepatitis B E antigen reagent 2;

[0110] 2) HBeAg antigen receptor particles were diluted to 100 μg / ml with PBS buffer as hepatitis B E antibody reagent 1, biotin-labeled HBeAg antigen was diluted to 1 μg / ml with PBS buffer as hepatitis B E antibody reagent 2, and neutralized E antigen was diluted to 20 μg / ml with PBS buffer as hepatitis B E antibody reagent 3.

[0111] 3) Assemble the hepatitis B E antigen reagent 1 and the hepatitis B E antigen reagent 2 into a complete hepatitis B E antigen reagent, and place them together with the photosensitive microsphere solution in a hepatitis B E antigen reagent kit (HBeAg).

[0112] 4) Assemble the Hepatitis B E antibody reagent 1 and the Hepatitis B E antibody reagent 2 into a complete Hepatitis B E antibody reagent, and place them together with the photosensitive microsphere solution in a Hepatitis B E antibody kit (HBeAb).

[0113] 5. Experimental data

[0114] Produced by Kemei Diagnostics The prepared hepatitis B E antigen reagent and hepatitis B E antibody reagent were tested by Smart photochemiluminescence analyzer, and commercially available negative samples, positive samples, and gray zone samples were used as test samples.

[0115] When the concentration value of the hepatitis B E antibody reagent is ≤1S / CO, the sample result is judged to be positive; otherwise it is judged to be negative; when the concentration value of the hepatitis B E antigen reagent is ≥1S / CO, the sample result is judged to be positive; otherwise it is judged to be negative.

[0116] The experimental data are shown in Appendix 2.

[0117]

[0118]

[0119] From the experimental data we can see that:

[0120] 3. When the HBV E antigen reagent and the HBV E antibody reagent are tested at the same time, and the HBV E antibody reagent is placed before the HBV E antigen reagent for testing; both sets of reagents are not interfered with, and the test results are similar to those of individual tests.

[0121] 4. When the hepatitis B virus E antigen reagent and the hepatitis B virus E antibody reagent are tested at the same time, and the hepatitis B virus E antigen reagent is placed before the hepatitis B virus E antibody reagent, the test result increases significantly, and the hepatitis B virus E antibody reagent is interfered by the contamination carried by the reagent.

[0122] The present embodiment provides an operation control device for detection items, which is applied to a sample analyzer, and includes: an acquisition module, used to acquire an execution list for at least two detection items; a judgment module, used to judge whether the execution list contains a specified detection item pair; and an adjustment module, used to control the two detection items in the specified detection item pair to be executed in a preset order when it is determined that the execution list contains a specified detection item pair.

[0123] The operation control device for the detection items of this embodiment may also include a processor and a memory, and the processor is used to execute the above-mentioned program modules stored in the memory to realize the operation control of the detection items and control the two detection items in the specified detection item pair to be executed in a preset order.

[0124] It should be noted that, although several units / modules or subunits / modules of the operation control device of the detection project are mentioned in the detailed description above, this division is merely exemplary and not mandatory. In fact, according to an embodiment of the present invention, the features and functions of two or more units / modules described above can be embodied in one unit / module. Conversely, the features and functions of one unit / module described above can also be further divided into multiple units / modules to be embodied.

[0125] This embodiment provides a storage medium storing a computer program. When the computer program is executed by a processor, the steps of the method for controlling the operation of the detection item described above or the steps of the method for controlling the calling of the reagent kit described above are executed.

[0126] The computer program may be implemented in any combination of one or more storage media, which may be readable signal media or readable storage media.

[0127] The readable storage medium may include, for example, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, device or device, or any combination thereof. More specific examples of readable storage media (a non-exhaustive list) may include: an electrical connection with one or more conductors, a portable disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination thereof.

[0128] The readable signal medium may include a data signal propagated in baseband or as part of a carrier wave, wherein a readable computer program is carried. Such propagated data signals may take a variety of forms, for example, may include electromagnetic signals, optical signals, or any suitable combination of the above. The readable signal medium may also be any storage medium other than a readable storage medium, which may send, propagate, or transmit a program for use by or in conjunction with an instruction execution system, apparatus, or device.

[0129] The computer program contained on the storage medium may be transmitted using any appropriate medium, including, for example, wireless, wired, optical cable, RF, etc., or any suitable combination of the above.

[0130] The computer program for performing the operation of the present invention may be written in any combination of one or more programming languages. The programming language may include an object-oriented programming language, such as Java, C++, etc., and may also include a conventional procedural programming language, such as "C" language or similar programming languages. The computer program may be executed entirely on the user computing device, partially on the user device, or entirely on a remote computing device or server. In the case of a remote computing device, the remote computing device may be connected to the user computing device through any type of network (e.g., it may include a local area network or a wide area network), or it may be connected to an external computing device (e.g., using an Internet service provider to connect through the Internet).

[0131] In one embodiment, the computing device may include one or more processors (CPU), input / output interfaces, network interfaces, and memory.

[0132] The memory may include non-permanent storage in a computer-readable medium, random access memory (RAM) and / or non-volatile memory in the form of read-only memory (ROM) or flash memory (FLASH RAM). The memory is an example of a computer-readable medium.

[0133] This embodiment provides a sample analyzer, including:

[0134] A reagent unit, including a reagent compartment for storing the detection reagent and a pipette for aspirating the detection reagent;

[0135] A sample unit, comprising a sample chamber for storing samples and a sample loading arm for aspirating samples;

[0136] an analysis unit for analyzing a mixture of a sample and a reagent;

[0137] A control device, used to control the sample analyzer, wherein the control device includes a database in which a list of designated detection item pairs is stored;

[0138] The control device also includes a readable storage medium of the present application, on which a computer program is stored for executing the steps of the operation control method of the detection item as described above or the steps of the calling control method of the reagent kit as described above.

[0139] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. When the terms "include" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or their combinations.

[0140] It should be noted that the terms "first", "second", etc. in the specification, claims and drawings of this application are used to distinguish similar objects, rather than to describe a specific order or sequence. It should be understood that the terms used in this way can be interchangeable under appropriate circumstances.

[0141] It should be understood that the exemplary embodiments in this specification can be implemented in a variety of different forms and should not be interpreted as being limited to the embodiments described herein. Additionally or alternatively, certain steps may be omitted, multiple steps may be combined into one step, and / or one step may be decomposed into multiple steps. These embodiments are provided to make the disclosure of this application thorough and complete, and to fully convey the concepts of these exemplary embodiments to those of ordinary skill in the art, and should not be construed as limitations on the present invention.

[0142] Although the spirit and principle of the present invention have been described with reference to several specific embodiments, it should be understood that the present invention is not limited to the disclosed specific embodiments, and the division of various aspects does not mean that the features in these aspects cannot be combined to benefit, and such division is only for the convenience of expression. The present invention is intended to cover various modifications and equivalent arrangements included in the spirit and scope of the attached claims.

Claims

1. A method for controlling the operation of a detection project, characterized in that: include: Get an execution list containing at least two detection items; Determining whether the execution list contains a specified detection item pair; When it is determined that the execution list includes a designated detection item pair, two detection items in the designated detection item pair are controlled to be executed in a preset order.

2. The operation control method of the detection item according to claim 1, characterized in that: Determining whether the execution list contains a specified detection item pair includes: Get the preset list of specified detection item pairs; Any two detection items in the execution list are matched with a preset list of designated detection item pairs, and it is determined whether the execution list contains the designated detection item pair according to the matching result.

3. The operation control method of the detection item according to claim 1, characterized in that: In the case where the execution list includes the designated detection item pair, the designated detection item pair is executed in the preset order only when two detection items in the designated detection item pair are adjacent to each other in the execution list.

4. The operation control method of the detection item according to claim 3, characterized in that: The specified detection item pair list includes: A plurality of groups of designated test item pairs and a preset order of executing the two test items corresponding to each group of designated test item pairs; Controlling the two test items in the specified test item pair to be executed in a preset order includes: Control the two test items in the specified test item pair to be executed according to the corresponding preset order in the specified test item pair list, and The execution order of other detection items in the execution list remains unchanged.

5. The operation control method of the detection item according to claim 1, characterized in that: When the two detection items in the designated detection item pair are controlled to be performed in a preset order, the pipette does not perform enhanced washing between sequentially aspirating detection reagents for the two detection items.

6. The operation control method of the detection item according to claim 1, characterized in that: The designated test item pair includes: two test items with cross contamination; Wherein, the cross contamination includes mutual consumption between detection reagents, and the mutual consumption includes at least one of the following: mutual binding and mutual reaction.

7. The operation control method of the detection item according to any one of claims 1 to 6, characterized in that: The two test items in the designated test item pair include an antibody test item for detecting antibodies and an antigen test item for detecting antigens corresponding to the antibodies; Furthermore, the preset sequence includes: executing the antibody detection item first, and then executing the antigen detection item.

8. The operation control method of the detection item according to claim 7, characterized in that: When the designated test item pair includes hepatitis B virus e antibody test and hepatitis B virus e antigen test, the preset sequence includes: Perform the hepatitis B virus e antibody test first, then perform the hepatitis B virus e antigen test.

9. The operation control method of the detection item according to claim 7, characterized in that: When the designated test item pair includes hepatitis B virus surface antibody test and hepatitis B virus surface antigen test, the preset sequence includes: Perform the hepatitis B virus surface antibody test first, then perform the hepatitis B virus surface antigen test.

10. A readable storage medium having a computer program stored thereon, wherein when the computer program is executed, the steps of the operation control method of the detection item according to any one of claims 1 to 9 are executed.

11. A sample analyzer, characterized in that: include: A reagent unit, including a reagent compartment for storing the detection reagent and a pipette for aspirating the detection reagent; A sample unit, comprising a sample chamber for storing samples and a sample loading arm for aspirating samples; an analysis unit for analyzing a mixture of a sample and a reagent; A control device, used to control the sample analyzer, wherein the control device includes a database in which a list of designated detection item pairs is stored; The control device further comprises a readable storage medium as claimed in claim 10, which is used to execute the steps of the operation control method of the detection item as claimed in any one of claims 1 to 9.

Images